Project Summary Physical injuries resulting from battlefield trauma present some of the greatest challenges for reconstruction. The best replacement for these wounds is uninjured autologous living tissue. Current clinical methods are effective for transferring this type of tissue. However, the methods are extremely limited by a lack of appropriate specialized tissue. Tissue engineering has shown promise for the reconstruction of complex physical injuries. The volume of tissue that can be engineered is limited by the extent to which stable blood vessels can be stimulated to form within the implanted material. The goals of this research are to optimize PEG hydrogel conditions to stimulate extensive and stable vessel formation in vivo and to use these hydrogels to increase the volume of vascularized bone that can be engineered for reconstruction of complex skeletal defects These goals are driven by the hypotheses that 1) the speed of endothelial cell migration and invasion is higher within macroporous hydrogels than hydrogels degraded only by cell proteolysis, 2) vessel stability is increased in materials that degrade and release growth factors after vessel invasion, and 3) increasing vascularization in chambers implanted against the periosteum will increase the volume and depth of osteogenesis. These hypotheses will be addressed by completing the following objectives: Specific Objective 1: Identify optimal PEG conditions that permit rapid cell and blood vessel invasion. Specific Objective 2: Identify the effects of material degradation and growth factor release kinetics on vessel persistence and maturation in implanted hydrogels. Specific Objective 3: Quantify the ability of hydrogels that stimulate rapid, stable neovascularization to promote vascularized bone formation in an animal model of guided tissue fabrication and determine whether addition of an osteogenic factor to the hydrogels further enhances bone formation. Completion of theses studies will lead to improved methods for engineering large volume tissues for the treatment of complex wounds resulting from battlefield trauma, civilian trauma, and tumor resection. PUBLIC HEALTH RELEVANCE: Project Narrative Relevance Physical injuries resulting from battlefield trauma present some of the greatest challenges for reconstruction. Tissue engineering has shown promise for the reconstruction of these complex wounds. The volume of tissue that can be engineered is limited by the extent to which stable blood vessels can be stimulated to form within the implanted material. The goal of this research is to design new biomaterials that stimulate blood vessel formation. These materials have the potential to improve the reconstruction and replacement of physical injuries suffered by veterans returning from current conflicts in Iraq and Afghanistan.